The central goal of this project will be to develop active interfaces between arrays of addressable nanowire electronic devices and cells to create two- and three-dimensional functional biomaterials. The nanoscale represents a natural length scale for devices used to create active interfaces to cells because biological nanostructures are the key components that define intercellular communication and signaling in living systems, yet this scale of interface is virtually uncharted research territory. The overall objectives that will be explored to address this territory and to meet the central project goal are as follows. First, limits of nanowire nanoelectronic device/cell interface functionality and sensitivity will be characterized. Communication with cells, both recording from (cell output) and stimulation of (cell input), through direct electrical mechanisms and chemical/biological signal detection/release will be developed and the corresponding detection sensitivity and spatial resolution for different modes will be elucidated. Second, addressable arrays of different types of functional nanowire devices interfaced with cellular networks will be developed and their behavior delineated. An important emphasis of this work, which exploits the unique capabilities of bottom-up versus top-down nanoscience, will be to develop (i) interfaced nanoelectronic arrays on flexible, biocompatible polymeric substrates, (ii) folded or layered nanowire/cell three-dimensional arrays using perforated polymeric substrates to enhance layer-to-layer interactions, and (iii) nanoelectronic devices projecting out of the substrate plane to enable interfacing `into' three-dimensional cellular arrays and tissue. The proposed project has the potential to impact biomedical research in substantial ways, including the establishment of powerful new tools for understanding the behavior of interacting cellular networks, the development of sophisticated, electrically-based cell/tissue interfaces for prosthetics and other medical devices, and the creation of new biomaterials with potential for diverse applications, such as in hybrid information processing.